GLOBAL INITIATIVE FOR CHRONIC OBSTRUCTIVE LUNG DISEASE (GOLD):

Transcription

1 GLOBAL INITIATIVE FOR CHRONIC OBSTRUCTIVE LUNG DISEASE (GOLD): Dr Bita Hajian Pneumoloog UZA

2 G O lobal Initiative for Chronic bstructive L D ung isease

3 Global Strategy for Diagnosis, Management and Prevention of COPD, 2016: Chapters Definition and Overview Diagnosis and Assessment Therapeutic Options Manage Stable COPD Manage Exacerbations Manage Comorbidities Updated 2015

4 Global Strategy for Diagnosis, Management and Prevention of COPD, 2015: Chapters Definition and Overview Diagnosis and Assessment Therapeutic Options Manage Stable COPD Manage Exacerbations Manage Comorbidities Updated 2015 Asthma COPD Overlap Syndrome (ACOS)

5 Definition of COPD COPD, a common preventable and treatable disease, is characterized by persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases. Exacerbations and comorbidities contribute to the overall severity in individual patients.

6 Mechanisms Underlying Airflow Limitation in COPD Small Airways Disease Airway inflammation Airway fibrosis, luminal plugs Increased airway resistance Parenchymal Destruction Loss of alveolar attachments Decrease of elastic recoil AIRFLOW LIMITATION

7 Professor Peter J. Barnes, MD National Heart and Lung Institute, London UK

8 Professor Peter J. Barnes, MD National Heart and Lung Institute, London UK

9 Professor Peter J. Barnes, MD National Heart and Lung Institute, London UK

10 Professor Peter J. Barnes, MD National Heart and Lung Institute, London UK

11 Burden of COPD COPD is a leading cause of morbidity and mortality worldwide. The burden of COPD is projected to increase in coming decades due to continued exposure to COPD risk factors and the aging of the world s population.

12 Risk Factors for COPD Genes Exposure to particles Tobacco smoke Occupational dusts, organic and inorganic Indoor air pollution from heating and cooking with biomass in poorly ventilated dwellings Outdoor air pollution Lung growth and development Gender Age Respiratory infections Socioeconomic status Asthma/Bronchial hyperreactivity Chronic Bronchitis

13 Risk Factors for COPD Genes Infections Socio-economic status Aging Populations

14 Global Strategy for Diagnosis, Management and Prevention of COPD, 2015: Chapters Definition and Overview Diagnosis and Assessment Therapeutic Options Manage Stable COPD Manage Exacerbations Manage Comorbidities Updated 2015

15 Diagnosis and Assessment: Key Points A clinical diagnosis of COPD should be considered in any patient who has dyspnea, chronic cough or sputum production, and a history of exposure to risk factors for the disease. Spirometry is required to make the diagnosis; the presence of a post-bronchodilator FEV 1 /FVC < 0.70 confirms the presence of persistent airflow limitation and thus of COPD.

16 Diagnosis and Assessment: Key Points The goals of COPD assessment are to determine the severity of the disease, including the severity of airflow limitation, the impact on the patient s health status, and the risk of future events. Comorbidities occur frequently in COPD patients, and should be actively looked for and treated appropriately if present.

17 Diagnosis of COPD SYMPTOMS shortness of breath chronic cough sputum EXPOSURE TO RISK FACTORS tobacco occupation indoor/outdoor pollution è SPIROMETRY: Required to establish diagnosis

18 Assessment of Airflow Limitation: Spirometry Spirometry should be performed after the administration of an adequate dose of a shortacting inhaled bronchodilator to minimize variability. A post-bronchodilator FEV 1 /FVC < 0.70 confirms the presence of airflow limitation. Where possible, values should be compared to age-related normal values to avoid overdiagnosis of COPD in the elderly.

19 Spirometry: Normal Trace Showing FEV 1 and FVC 5 FVC Volume, liters FEV 1 = 4L FVC = 5L FEV 1 /FVC = Time, sec

20 Spirometry: Obstructive Disease 5 Normal 4 Volume, liters FEV 1 = 1.8L FVC = 3.2L FEV 1 /FVC = 0.56 Obstructive Time, seconds

21 Assessment of COPD Assess symptoms Assess degree of airflow limitation using spirometry Assess risk of exacerbations Assess comorbidities

22 Symptoms of COPD The characteristic symptoms of COPD are chronic and progressive dyspnea, cough, and sputum production that can be variable from day-to-day. Dyspnea: Progressive, persistent and characteristically worse with exercise. Chronic cough: May be intermittent and may be unproductive. Chronic sputum production: COPD patients commonly cough up sputum.

23 Classification of Severity of Airflow Limitation in COPD* In patients with FEV 1 /FVC < 0.70: GOLD 1: Mild GOLD 2: Moderate GOLD 3: Severe GOLD 4: Very Severe FEV 1 > 80% predicted 50% < FEV 1 < 80% predicted 30% < FEV 1 < 50% predicted FEV 1 < 30% predicted *Based on Post-Bronchodilator FEV 1

24 Assessment of COPD Assess symptoms Assess degree of airflow limitation using spirometry COPD Assessment Test (CAT) Assess risk of exacerbations Assess comorbidities or Clinical COPD Questionnaire (CCQ) or mmrc Breathlessness scale

25 Assessment of Symptoms COPD Assessment Test (CAT): An 8-item measure of health status impairment in COPD ( Clinical COPD Questionnaire (CCQ): Selfadministered questionnaire developed to measure clinical control in patients with COPD (

26 Assessment of Symptoms Breathlessness Measurement using the Modified British Medical Research Council (mmrc) Questionnaire: relates well to other measures of health status and predicts future mortality risk.

27 Modified MRC (mmrc)questionnaire

28 Assessment of COPD Assess symptoms Assess degree of airflow limitation using spirometry Assess risk of exacerbations Use spirometry for grading severity Assess comorbidities according to spirometry, using four grades split at 80%, 50% and 30% of predicted value

29 Assessment of COPD Assess symptoms Assess degree of airflow limitation using spirometry Assess risk of exacerbations Assess comorbidities Use history of exacerbations and spirometry. Two exacerbations or more within the last year or an FEV 1 < 50 % of predicted value are indicators of high risk. Hospitalization for a COPD exacerbation associated with increased risk of death.

30 Assess Risk of Exacerbations To assess risk of exacerbations use history of exacerbations and spirometry: Two or more exacerbations within the last year or an FEV 1 < 50 % of predicted value are indicators of high risk. One or more hospitalizations for COPD exacerbation should be considered high risk.

31 Combined Assessment of COPD Assess symptoms Assess degree of airflow limitation using spirometry Assess risk of exacerbations Combine these assessments for the purpose of improving management of COPD

32 Risk (GOLD Classification of Airflow Limitation)) Risk (Exacerbation history) Global Strategy for Diagnosis, Management and Prevention of COPD Combined Assessment of COPD 4 3 (C) (D) 2 or > 1 leading to hospital admission 2 1 (A) (B) CAT < 10 CAT > 10 Symptoms mmrc 0 1 mmrc > 2 Breathlessness 1 (not leading to hospital admission) 0

33 Combined Assessment of COPD Assess symptoms first (C) (D) If CAT < 10 or mmrc 0-1: Less Symptoms/breathlessness (A or C) (A) (B) CAT < 10 CAT > 10 Symptoms mmrc 0 1 mmrc > 2 Breathlessness If CAT > 10 or mmrc > 2: More Symptoms/breathlessness (B or D)

34 Risk (GOLD Classification of Airflow Limitation) Risk (Exacerbation history) Global Strategy for Diagnosis, Management and Prevention of COPD Combined Assessment of COPD Assess risk of exacerbations next 4 3 (C) (D) 2 or > 1 leading to hospital admission If GOLD 3 or 4 or 2 exacerbations per year or > 1 leading to hospital admission: High Risk (C or D) 2 1 (A) (B) CAT < 10 CAT > 10 Symptoms 1 (not leading to hospital admission) 0 If GOLD 1 or 2 and only 0 or 1 exacerbations per year (not leading to hospital admission): Low Risk (A or B) mmrc 0 1 mmrc > 2 Breathlessness

35 Risk (GOLD Classification of Airflow Limitation)) Risk (Exacerbation history) Global Strategy for Diagnosis, Management and Prevention of COPD Combined Assessment of COPD 4 3 (C) (D) 2 or > 1 leading to hospital admission 2 1 (A) (B) CAT < 10 CAT > 10 Symptoms mmrc 0 1 mmrc > 2 Breathlessness 1 (not leading to hospital admission) 0

36 Global Strategy for Diagnosis, Management and Prevention of COPD Combined Assessment of COPD When assessing risk, choose the highest risk according to GOLD grade or exacerbation history. One or more hospitalizations for COPD exacerbations should be considered high risk.) Patient Characteristic Spirometric Classification Exacerbations per year CAT mmrc A B C D Low Risk Less Symptoms Low Risk More Symptoms High Risk Less Symptoms High Risk More Symptoms GOLD < GOLD > 10 > 2 GOLD 3-4 > 2 < GOLD 3-4 > 2 > 10 > 2

37 Assess COPD Comorbidities COPD patients are at increased risk for: Cardiovascular diseases Osteoporosis Respiratory infections Anxiety and Depression Diabetes Lung cancer Bronchiectasis These comorbid conditions may influence mortality and hospitalizations and should be looked for routinely, and treated appropriately.

38 Global Strategy for Diagnosis, Management and Prevention of COPD, 2015: Chapters Definition and Overview Diagnosis and Assessment Therapeutic Options Manage Stable COPD Manage Exacerbations Manage Comorbidities Updated 2015

39 Therapeutic Options: Key Points Smoking cessation has the greatest capacity to influence the natural history of COPD. Health care providers should encourage all patients who smoke to quit. Pharmacotherapy and nicotine replacement reliably increase long-term smoking abstinence rates. All COPD patients benefit from regular physical activity and should repeatedly be encouraged to remain active.

40 Therapeutic Options: COPD Medications Beta 2 -agonists Short-acting beta 2 -agonists Long-acting beta 2 -agonists Anticholinergics Short-acting anticholinergics Long-acting anticholinergics Combination short-acting beta 2 -agonists + anticholinergic in one inhaler Combination long-acting beta 2 -agonist + anticholinergic in one inhaler Methylxanthines Inhaled corticosteroids Combination long-acting beta 2 -agonists + corticosteroids in one inhaler Systemic corticosteroids Phosphodiesterase-4 inhibitors

41 Therapeutic Options: Inhaled Corticosteroids Regular treatment with inhaled corticosteroids improves symptoms, lung function and quality of life and reduces frequency of exacerbations for COPD patients with an FEV 1 < 60% predicted. Inhaled corticosteroid therapy is associated with an increased risk of pneumonia. Withdrawal from treatment with inhaled corticosteroids may lead to exacerbations in some patients.

42 Therapeutic Options: Combination Therapy An inhaled corticosteroid combined with a long-acting beta 2 -agonist is more effective than the individual components in improving lung function and health status and reducing exacerbations in moderate to very severe COPD. Combination therapy is associated with an increased risk of pneumonia. Addition of a long-acting beta 2 -agonist/inhaled glucorticosteroid combination to an anticholinergic (tiotropium) appears to provide additional benefits.

43 Therapeutic Options: Systemic Corticosteroids Chronic treatment with systemic corticosteroids should be avoided because of an unfavorable benefit-torisk ratio.

44 Therapeutic Options: Phosphodiesterase-4 Inhibitors In patients with severe and very severe COPD (GOLD 3 and 4) and a history of exacerbations and chronic bronchitis, the phospodiesterase-4 inhibitor, roflumilast, reduces exacerbations treated with oral glucocorticosteroids.

45 Therapeutic Options: Other Pharmacologic Treatments Influenza vaccines can reduce serious illness. Pneumococcal polysaccharide vaccine is recommended for COPD patients 65 years and older and for COPD patients younger than age 65 with an FEV 1 < 40% predicted. The use of antibiotics, other than for treating infectious exacerbations of COPD and other bacterial infections, is currently not indicated.

46 Therapeutic Options: Rehabilitation All COPD patients benefit from exercise training programs with improvements in exercise tolerance and symptoms of dyspnea and fatigue. Although an effective pulmonary rehabilitation program is 6 weeks, the longer the program continues, the more effective the results. If exercise training is maintained at home, the patient's health status remains above prerehabilitation levels.

47 Therapeutic Options: Other Treatments Oxygen Therapy: The long-term administration of oxygen (> 15 hours per day) to patients with chronic respiratory failure has been shown to increase survival in patients with severe, resting hypoxemia. Ventilatory Support: Combination of noninvasive ventilation (NIV) with long-term oxygen therapy may be of some use in a selected subset of patients, particularly in those with pronounced daytime hypercapnia.

48 Global Strategy for Diagnosis, Management and Prevention of COPD, 2015: Chapters Definition and Overview Diagnosis and Assessment Therapeutic Options Manage Stable COPD Manage Exacerbations Manage Comorbidities Updated 2015

49 Manage Stable COPD: Key Points Long-term monotherapy with oral or inhaled corticosteroids is not recommended in COPD. The phospodiesterase-4 inhibitor roflumilast may be useful to reduce exacerbations for patients with FEV 1 < 50% of predicted, chronic bronchitis, and frequent exacerbations.

50 Manage Stable COPD: All COPD Patients Avoidance of risk factors - smoking cessation - reduction of indoor pollution - reduction of occupational exposure Influenza vaccination

51 STUDY AIM Roflumilast on top of triple therapy (ICS/LABA/LAMA)

52 STUDY AIM The primary objective of this study is to evaluate the possible use of CT based functional respiratory imaging (FRI) on the phenotyping of severe COPD patients after a 6 month treatment with Roflumilast Secondary outcome variables are health related quality of life, lung function tests and exercise tolerance. Roflumilast on top of triple therapy (ICS/LABA/LAMA)

53 FUNCTIONAL RESPIRATORY IMAGING (FRI) scan segment simulate flow

54 FRI OUTCOME Perfusion and tissue Ventilation Deposition

55 Ventilation CHANGES IN FRI OUTCOME

56 CHANGES IN FRI OUTCOME Blood vessel volume pre [ml] post [ml] change [%] RUL RML RLL LUL LLL Perfusion and tissue

57 Deposition CHANGES IN FRI OUTCOME

58 STUDY DESIGN Double blind placebo controlled design Block randomization 3 Roflumilast/ 1 placebo Inclusion period: ±10 months (jan-oct 2012) 41 included COPD GOLD III and IV patients 9 drop-outs 32 evaluable patients 32 evaluable patients 23 treated with Roflumilast on top of ICS/LABA/LAMA 9 treated with placebo on top of ICS/LABA/LAMA

59 CHANGE IN FEV1 Significant improvement in FEV1 in Roflumilast group (+66ml) compared to drop in placebo (-59ml) p=0.006 p=0.01 p=0.052

60 CHANGE IN FEV1 8 patients (35%) in the Roflumilast group have a FEV1 response > 120ml* (+ 186 ml on average) Responders are the patients who feel at baseline significantly worse after 6MWT compared to nonresponders in terms of Borg score Dynamic hyperinflation? p=0.013 Does Roflumilast cause a signal in hyperinflation? *Quality and reproducibility of spirometry in COPD patients in a randomized trial (UPLIFT). Janssens W et al. Respir Med May 25.

61 MODE OF ACTION OF ROFLUMILAST More blood vessels in lobe More reduction in hyperinflation

62 MODE OF ACTION OF ROFLUMILAST Orally administered Roflumilast reaches areas undertreated with inhaled medication Reduction in regional hyperinflation Redistribution of internal airflow distribution Redistribution of inhaled ICS/LABA/LAMA Additional improvement in FEV1, exercise tolerance,

63 Global Strategy for Diagnosis, Management and Prevention of COPD, 2015: Chapters n n n n n n Definition and Overview Diagnosis and Assessment Therapeutic Options Manage Stable COPD Manage Exacerbations Manage Comorbidities Updated 2015

64 Manage Exacerbations An exacerbation of COPD is: an acute event characterized by a worsening of the patient s respiratory symptoms that is beyond normal dayto-day variations and leads to a change in medication.

65 Professor P.J. Barnes, MD, National Heart and Lung Institute, London UK

66 Manage Exacerbations: Key Points The most common causes of COPD exacerbations are viral upper respiratory tract infections and infection of the tracheobronchial tree. Diagnosis relies exclusively on the clinical presentation of the patient complaining of an acute change of symptoms that is beyond normal day-today variation. The goal of treatment is to minimize the impact of the current exacerbation and to prevent the development of subsequent exacerbations.

67 Manage Exacerbations: Key Points Short-acting inhaled beta 2 -agonists with or without short-acting anticholinergics are usually the preferred bronchodilators for treatment of an exacerbation. Systemic corticosteroids and antibiotics can shorten recovery time, improve lung function (FEV 1 ) and arterial hypoxemia (PaO 2 ), and reduce the risk of early relapse, treatment failure, and length of hospital stay.

68 Consequences Of COPD Exacerbations Negative impact on quality of life Impact on symptoms and lung function Accelerated lung function decline EXACERBATIONS Increased Mortality Increased economic costs

69 Manage Exacerbations: Treatment Options Oxygen: titrate to improve the patient s hypoxemia with a target saturation of 88-92%. Bronchodilators: Short-acting inhaled beta 2 -agonists with or without short-acting anticholinergics are preferred. Systemic Corticosteroids: Shorten recovery time, improve lung function (FEV 1 ) and arterial hypoxemia (PaO 2 ), and reduce the risk of early relapse, treatment failure, and length of hospital stay. A dose of 40 mg prednisone per day for 5 days is recommended.

70 Manage Exacerbations: Treatment Options Noninvasive ventilation (NIV) for patients hospitalized for acute exacerbations of COPD: Improves respiratory acidosis, decreases respiratory rate, severity of dyspnea, complications and length of hospital stay. Decreases mortality and needs for intubation. GOLD Revision 2011

71 Global Strategy for Diagnosis, Management and Prevention of COPD, 2015: Chapters n n n n n n Definition and Overview Diagnosis and Assessment Therapeutic Options Manage Stable COPD Manage Exacerbations Manage Comorbidities Updated 2015

72 Manage Comorbidities COPD often coexists with other diseases (comorbidities) that may have a significant impact on prognosis. In general, presence of comorbidities should not alter COPD treatment and comorbidities should be treated as if the patient did not have COPD.

73 Manage Comorbidities Cardiovascular disease (including ischemic heart disease, heart failure, atrial fibrillation, and hypertension) is a major comorbidity in COPD and probably both the most frequent and most important disease coexisting with COPD.

74 Manage Comorbidities Osteoporosis and anxiety/depression: often underdiagnosed and associated with poor health status and prognosis. Lung cancer: frequent in patients with COPD; the most frequent cause of death in patients with mild COPD. Serious infections: respiratory infections are especially frequent. Metabolic syndrome and manifest diabetes: more frequent in COPD and the latter is likely to impact on prognosis.